Glomerular function and morphology in puromycin aminonucleoside nephropathy in rats.

BACKGROUND The most characteristic manifestation of minimal-change nephropathy is podocyte cell process broadening. In a previous study in children from our unit, we found an inverse correlation between foot process width, glomerular filtration rate (GFR), and filtration fraction. The aim of the present study was to determine whether this relationship also existed in the puromycin aminonucleoside (PAN) experimental model. METHODS Sixteen Munich-Wistar-Frömter male rats initially weighing median 247 g (range 171-286) were used. Four rats served as controls. The other 12 rats were divided into three groups receiving daily subcutaneous injections of 1, 1.67, and 2.5 mg PAN/100 g body weight respectively, for 6 days. GFR was determined by clearance of inulin and the fractional urine albumin excretion was measured. Standard stereological methods were used to estimate the glomerular volume, the mean foot process width and the length density of slit pores. RESULTS GFR decreased with increasing PAN doses. The glomerular volume was increased in the group receiving the lowest PAN dose, while it was decreased in the group with the highest PAN dose, compared with controls. The fractional albumin excretion and the foot process width increased and the total slit pore length decreased with increasing doses of PAN. GFR correlated directly with the glomerular volume as did the foot process width with the fractional albumin excretion. The foot process width correlated inversely with the glomerular volume as did the glomerular volume with the fractional albumin excretion, and GFR with foot process width. CONCLUSIONS The decreased GFR found in the nephrotic rats was inversely related to foot process width and directly related to glomerular volume, confirming our previous results in children in an early stage of the nephrotic syndrome.

[1]  M. Karnovsky,et al.  A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron-microscopy , 1965 .

[2]  L. Recant,et al.  Experimental aminonucleoside nephrosis in rats. , 1957, The Journal of laboratory and clinical medicine.

[3]  B. Myers,et al.  Determinants of glomerular hypofiltration in nephrotic patients with minimal change nephropathy. , 1994, Journal of the American Society of Nephrology : JASN.

[4]  A. Fogo,et al.  Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. , 1990, Kidney international.

[5]  R. Brunkhorst,et al.  Single nephron hyperfiltration and proteinuria in a newly selected rat strain with superficial glomeruli. , 1986, Renal physiology.

[6]  J. Mahan,et al.  Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis. , 1986, The American journal of pathology.

[7]  M. Kretzler,et al.  A frequent pathway to glomerulosclerosis: deterioration of tuft architecture-podocyte damage-segmental sclerosis. , 1996, Kidney & blood pressure research.

[8]  M. Farquhar,et al.  AN ELECTRON MICROSCOPE STUDY OF THE GLOMERULUS IN NEPHROSIS, GLOMERULONEPHRITIS, AND LUPUS ERYTHEMATOSUS , 1957, The Journal of experimental medicine.

[9]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[10]  U. Berg,et al.  Influence of serum albumin on renal function in nephrotic syndrome , 1999, Pediatric Nephrology.

[11]  U. Berg,et al.  Foot process fusion and glomerular filtration rate in minimal change nephrotic syndrome. , 1984, Kidney international.

[12]  J. Weening,et al.  Puromycin aminonucleoside and adriamycin disturb cytoskeletal and extracellular matrix protein organization, but not protein synthesis of cultured glomerular epithelial cells. , 1994, Experimental nephrology.

[13]  B. Brenner,et al.  Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit. , 1998, Journal of the American Society of Nephrology : JASN.

[14]  M. Karnovsky,et al.  An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. , 1975, Kidney international.

[15]  R. Habib,et al.  The primary nephrotic syndrome of childhood. Classification and clinicopathologic study of 406 cases. , 1971, Pathology annual.

[16]  H. Trachtman,et al.  Recombinant human growth hormone exacerbates chronic puromycin aminonucleoside nephropathy in rats. , 1993, Kidney international.

[17]  T. Meyer,et al.  Tubulointerstitial injury and impaired renal function after recovery from acute puromycin nephrosis. , 1995, American Journal of Physiology.

[18]  B. Maess,et al.  Species and strain differences in urinary protein excretion. , 1985, Renal physiology.

[19]  K. Gärtner,et al.  Distribution of glomeruli in the renal cortex of Munich Wistar Frömter (MWF) rats. , 1983, Renal physiology.

[20]  U. Berg,et al.  Renal hemodynamics in minimal change nephrotic syndrome in childhood. , 1982, The International journal of pediatric nephrology.

[21]  G. Remuzzi,et al.  Pathophysiologic implications of proteinuria in a rat model of progressive glomerular injury. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[22]  J. Bertram,et al.  Biphasic glomerular hypertrophy in rats administered puromycin aminonucleoside. , 1996, Kidney international.

[23]  Thickness estimation of fluorescent sections using a CSLM , 1996 .

[24]  J. Churg,et al.  Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. , 1970, Lancet.

[25]  B. Kristal,et al.  Structural basis for reduced glomerular filtration capacity in nephrotic humans. , 1994, The Journal of clinical investigation.

[26]  B. Brenner,et al.  Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules. , 1977, The Journal of clinical investigation.

[27]  G. Remuzzi,et al.  Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats. , 1988, Kidney international.

[28]  M. Farquhar,et al.  Alterations of the glomerular epithelium in acute aminonucleoside nephrosis. Evidence for formation of occluding junctions and epithelial cell detachment. , 1976, Laboratory investigation; a journal of technical methods and pathology.

[29]  Y. Tomino,et al.  Re-evaluation of foot process effacement in acute puromycin aminonucleoside nephrosis. , 1996, Kidney international.